Phenotypes associated with this allele

• Allele Symbol: Egr2^tm2(cre)Pch
• Allele Name: targeted mutation 2, Patrick Charnay
• Allele ID: MGI:1931056
• Summary: 15 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Egr2^tm2(cre)Pch/Egr2^+ Gt(ROSA)26Sor^tm8(Map2k1*,EGFP)Rsky/? Ptpn11^tm1.1Wbm/Ptpn11^tm1.1Wbm	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6	MGI:5588145
cn2	Egr2^tm2(cre)Pch/Egr2^+ Erbb2^tm1Cbm/Erbb2^tm2Cbm	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6	MGI:2177311
cn3	Egr2^tm2(cre)Pch/Egr2^+ Erbb2^tm2Cbm/Erbb2^tm2Cbm	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6	MGI:5524263
cn4	Egr2^tm2(cre)Pch/Egr2^+ Gt(ROSA)26Sor^tm7(Pik3ca*,EGFP)Rsky/? Ptpn11^tm1.1Wbm/Ptpn11^tm1.1Wbm	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6	MGI:5588148
cn5	Egr2^tm2(cre)Pch/Egr2^+ Ptpn11^tm1.1Wbm/Ptpn11^tm1.1Wbm	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL	MGI:4365548
cn6	Cacna1d^tm1Hgn/Cacna1d^tm1Hgn Egr2^tm2(cre)Pch/Egr2^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:5431134
cn7	Egr2^tm2(cre)Pch/Egr2^+ Robo3^tm1.1Ache/Robo3^tm1.1Ache	involves: 129S2/SvPas	MGI:4441336
cn8	Egr2^tm2(cre)Pch/? Gt(ROSA)26Sor^tm5(CAG-EGFP,-lacZ)Dym/? Tg(Fev-flpe)1Dym/?	involves: 129S2/SvPas	MGI:3804426
cn9	Egr2^tm2(cre)Pch/? Mnat1^tm2Tpm/Mnat1^tm2.1Tpm	involves: 129S2/SvPas	MGI:3707557
cn10	Egr2^tm2(cre)Pch/Egr2^+ Gt(ROSA)26Sor^tm7(Pik3ca*,EGFP)Rsky/?	involves: 129S2/SvPas * C57BL/6	MGI:5588141
cn11	Egr2^tm2(cre)Pch/Egr2^+ Gt(ROSA)26Sor^tm8(Map2k1*,EGFP)Rsky/?	involves: 129S2/SvPas * C57BL/6	MGI:5588113
cn12	Egr2^tm2(cre)Pch/Egr2^+ Robo3^tm1.1Ache/Robo3^tm1.1Ache Tg(Mnx1-EGFP)#Tmj/0	involves: 129S2/SvPas * C57BL/6 * DBA	MGI:4441376
cn13	Egr2^tm2(cre)Pch/Egr2^+ Phox2b^tm4Jbr/Phox2b^+	involves: 129S2/SvPas * C57BL/6 * DBA/2	MGI:5293367
cn14	Phox2b^tm3.1Jbr/Phox2b^tm3.1Jbr Egr2^tm2(cre)Pch/Egr2^+	involves: 129S2/SvPas * C57BL/6 * DBA/2	MGI:4418307
cn15	Crygn^tm1a(EUCOMM)Wtsi/Crygn^tm1a(EUCOMM)Wtsi Egr2^tm2(cre)Pch/Egr2^+	involves: 129S2/SvPas * C57BL/6N	MGI:5903403

Genotype
MGI:5588145

cn1

• Allelic Composition: Egr2^tm2(cre)Pch/Egr2⁺; Gt(ROSA)26Sor^{tm8(Map2k1*,EGFP)Rsky}/?; Ptpn11^tm1.1Wbm/Ptpn11^tm1.1Wbm
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

nervous system

hypermyelination ( J:207470 )

• mice show normal myelination at P15, however axons of peripheral nerves are hypermyelinated by P90

Genotype
MGI:2177311

cn2

• Allelic Composition: Egr2^tm2(cre)Pch/Egr2⁺; Erbb2^tm1Cbm/Erbb2^tm2Cbm
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:75421 )

• 5 of 37 die within 6 months

behavior/neurological

abnormal locomotor activation ( J:75421 )

• difficulties in hindlimb movement

abnormal gait ( J:75421 )

• gait abnormalities

growth/size/body

cachexia ( J:75421 )

• display wasting associated with weight loss and premature death

limbs/digits/tail

kinked tail ( J:75421 )

• kinked or serpentine tails

nervous system

decreased Schwann cell number ( J:75421 )

• at P3.5, see a 10-fold reduction in ventral and a 5-fold reduction in dorsal roots, with this reduction still apparent at P15, however by 6 months of age, cell numbers are similar to those in controls, however myelin sheaths formed are thin

abnormal myelin sheath morphology ( J:75421 )

• reduction in thickness of the myelin sheath of sciatic nerves at P15 that persists at 6 and 14 months of age

• thin myelin is due to the presence of fewer wraps of myelin around the axon

abnormal dorsal spinal root morphology ( J:75421 )

• dorsal roots display a severe decrease of Schwann cells in all mutants at P3.5 and P15

abnormal sciatic nerve morphology ( J:75421 )

• sciatic nerves at P15 are translucent and thin

abnormal ventral spinal root morphology ( J:75421 )

• ventral roots display a severe decrease of Schwann cells in all mutants at P3.5 and P15

• about 20% loss of axons in the L5 ventral root

abnormal myelination ( J:75421 )

• hypomyelination in sciatic, sural, saphenous nerves, nerves innervating lower leg muscles, and the dorsal spinal roots and absent myelin in ventral spinal roots

• occasionally see large-caliber axons lacking myelin that are still surrounded by a Schwann cell basal lamina in the sciatic nerve

Genotype
MGI:5524263

cn3

• Allelic Composition: Egr2^tm2(cre)Pch/Egr2⁺; Erbb2^tm2Cbm/Erbb2^tm2Cbm
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

nervous system

demyelination ( J:199150 )

• peripheral without Schwann cell turn-over

behavior/neurological

behavior/neurological phenotype ( J:199150 )

N • mice exhibit normal motor coordination

Genotype
MGI:5588148

cn4

• Allelic Composition: Egr2^tm2(cre)Pch/Egr2⁺; Gt(ROSA)26Sor^{tm7(Pik3ca*,EGFP)Rsky}/?; Ptpn11^tm1.1Wbm/Ptpn11^tm1.1Wbm
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

nervous system

abnormal myelination ( J:207470 )

• myelination defects are more pronounced than in single conditional Ptpn11^tm1.1Wbm homozygotes

Genotype
MGI:4365548

cn5

• Allelic Composition: Egr2^tm2(cre)Pch/Egr2⁺; Ptpn11^tm1.1Wbm/Ptpn11^tm1.1Wbm
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * SJL

nervous system

decreased motor neuron number ( J:153219 )

• in the ventral but not dorsal roots

abnormal myelination ( J:153219 , J:207470 )

• peripheral nerves are hypomyelinated with thinner myelin in axons with larger axon diameter (J:153219)

decreased nerve conduction velocity ( J:153219 )

• in the saphenous nerve

Genotype
MGI:5431134

cn6

• Allelic Composition: Cacna1d^tm1Hgn/Cacna1d^tm1Hgn; Egr2^tm2(cre)Pch/Egr2⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

hearing/vestibular/ear

abnormal auditory brainstem response waveform shape ( J:185977 )

• above 60 dB, the amplitudes of waves II and III are increased compared to in control mice

• between 50 and 75 dB, wave I amplitude if slightly decreased compared to in control mice

• however, mice exhibit normal ABR thresholds for pure tone stimuli and in response to click or noise burst stimuli

abnormal distortion product otoacoustic emission ( J:185977 )

• slightly reduced at 50 dB SPL f2

increased or absent distortion product otoacoustic emission threshold ( J:185977 )

• slightly increased threshold in the middle hearing range

nervous system

abnormal pons morphology ( J:185977 )

• the lateral superior olive is round not U shape as in control mice and reduced in volume due to reduced neuron number

• the medial nucleus of the trapezoid body is reduced in volume due to reduced neuron number compared to in control mice

decreased neuron number ( J:185977 )

• in the lateral superior olive and medial nucleus of the trapezoid body

Genotype
MGI:4441336

cn7

• Allelic Composition: Egr2^tm2(cre)Pch/Egr2⁺; Robo3^tm1.1Ache/Robo3^tm1.1Ache
• Genetic Background: involves: 129S2/SvPas

Reduced internuclear commissure in Robo3^tm1.1Ache/Robo3^tm1.1Ache Egr2^tm2(cre)Pch/Egr2⁺ mice

nervous system

abnormal brain commissure morphology ( J:158918 )

• at E11 - E12, a severe reduction of commissural projections in r3 and r5 is seen

• at E15 and in newborns, virtually no axons are found to cross the midline at the level of the abducens nuclei

abnormal innervation ( J:158918 )

• globular bushy cell projections from the anteroventral cochlear nucleus to the principal cells of the median nucleus of the trapezoid body are exclusively ipsilateral

behavior/neurological

abnormal reflex ( J:158918 )

• impairment in horizontal visual vestibuloocular reflex (VVOR) but not in vertical VVOR

abnormal optokinetic reflex ( J:158918 )

• impairment in horizontal OKR but not in vertical OKR

• defects occur predominantly in the low frequency range

abnormal horizontal vestibuloocular reflex ( J:158918 )

• impairment in horizontal VOR but not in vertical VOR

• defects in VOR are more predominant at high frequencies

hearing/vestibular/ear

abnormal horizontal vestibuloocular reflex ( J:158918 )

• impairment in horizontal VOR but not in vertical VOR

• defects in VOR are more predominant at high frequencies

abnormal auditory brainstem response ( J:158918 )

• 3 rather than 4 waves are present ipsilaterally and the third wave has a longer latency and is not followed by any identifiable wave

• the appearance of contralateral wave IVc is delayed compared to controls

Genotype
MGI:3804426

cn8

• Allelic Composition: Egr2^tm2(cre)Pch/?; Gt(ROSA)26Sor^{tm5(CAG-EGFP,-lacZ)Dym}/?; Tg(Fev-flpe)1Dym/?
• Genetic Background: involves: 129S2/SvPas

normal phenotype

no abnormal phenotype detected ( J:136096 )

• alleles are used in intersectional and subtractive cell lineage fate mapping to visualize serotonin (5-HT) producing neurons and their precursors in the E12.5 embryonic hindbrain or mature brainstem

• rhombomere-3 (r3) rhombomere-5 (r5) derived 5-HT precursor cells are labeled by beta-gal while 5-HT precursors arising outside of r3 or r5 are labeled by eGFP

Genotype
MGI:3707557

cn9

• Allelic Composition: Egr2^tm2(cre)Pch/?; Mnat1^tm2Tpm/Mnat1^tm2.1Tpm
• Genetic Background: involves: 129S2/SvPas

reproductive system

abnormal spermatogenesis ( J:120170 )

♂ • at 6 weeks of age, pyknotic germ cells in the seminiferous tubules in testis indicative of spermatogonia and spermatocyte cell death

♂ • at 10 weeks of age, severe wasting and dramatically reduced cellularity was visible macroscopically; entirely devoid of all germ cells and their derivatives

♂ • at 3 weeks of age, the developing germ lineage in the seminiferous tubules was completely indistinguishable from control animals

♂ • at 10 weeks of age, Sertoli cells in the seminiferous tubules and cells of interstitium were normal

behavior/neurological

abnormal gait ( J:120170 )

• exhibit a variety of symptoms of Schwann cell dysfunction including gait abnormalities beginning at 3 month of age

• mutant were viable and healthy and displayed no signs of neuropathy or myelin dysfunction into early adulthood up to 3 month of age

growth/size/body

decreased lean body mass ( J:120170 )

• beginning at 3 month of age, pronounced in the hind limbs suggestive of neuropathy and subsequent neurogenic muscular atrophy

nervous system

abnormal Schwann cell precursor morphology ( J:120170 )

• at 3 months of age, the mutant exhibited a marked increase in Schwann lineage proliferation

demyelination ( J:120170 )

• beginning at 3 month of age, large diameter axons completely denuded of myelin are present in sciatic nerves

• by 5 month of age, essentially all of the myelinated axons shows signs of extensive demyelination

• sciatic nerves from mutant animals at 1 month and 2 month of age showed normal myelin thickness compared to axonal diameter indicating myelinating Schwann cells are capable of attaining and a mature myelinated phenotype

Genotype
MGI:5588141

cn10

• Allelic Composition: Egr2^tm2(cre)Pch/Egr2⁺; Gt(ROSA)26Sor^{tm7(Pik3ca*,EGFP)Rsky}/?
• Genetic Background: involves: 129S2/SvPas * C57BL/6

nervous system

abnormal myelination ( J:207470 )

• myelination is impaired

Genotype
MGI:5588113

cn11

• Allelic Composition: Egr2^tm2(cre)Pch/Egr2⁺; Gt(ROSA)26Sor^{tm8(Map2k1*,EGFP)Rsky}/?
• Genetic Background: involves: 129S2/SvPas * C57BL/6

nervous system

abnormal myelin sheath morphology ( J:207470 )

• onion bulb structures are seen indicating myelin degeneration and regeneration

• however, stacking of myelin sheaths in compact myelin is unaffected

• noncompact myelin structures are more abundant

increased myelin sheath thickness ( J:207470 )

• myelin sheaths are thicker at P15 and P30 and myelin continues to grow radially such that the mean myelin area in peripheral nerves at P90 is increased 6-fold

• increase in myelin thickness is particularly pronounced in small-diameter fibers

tomacula ( J:207470 )

• aberrant paranodal myelin (tomaculi) and infolded myelin loops

abnormal sciatic nerve morphology ( J:207470 )

• increase in the diameter of sciatic nerves due to massive hypermyelination and reduced axonal packing

hypermyelination ( J:207470 )

• myelination begins prematurely and mice show continuous myelin growth

• increase in the number of myelinated fibers per field at P0

• myelin abnormalities are seen at P30-P90 but not at P15, indicating that they result from massive hypermylination

• treatment with the mTORC1 inhibitor everolimus dampens myelin growth in the nerves of mutants and completely rescues the decreased axonal packing

abnormal nerve conduction ( J:207470 )

• ratio of compound action potentials in myelinated A and nonmyelinated C fibers (A/C fiber waves) is reduced and there is a reduction in numbers of active mechanoreceptive units after P60 indicating that many myelinated axons are not conducting

increased nerve conduction velocity ( J:207470 )

• D-hair mechanoreceptors show increased conduction velocities at P30, however no differences were seen after P60

• however, conduction velocities of other mechanosensory fibers are unchanged

Genotype
MGI:4441376

cn12

• Allelic Composition: Egr2^tm2(cre)Pch/Egr2⁺; Robo3^tm1.1Ache/Robo3^tm1.1Ache; Tg(Mnx1-EGFP)#Tmj/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * DBA

nervous system

abnormal pons morphology ( J:158918 )

• at E14, the abducens motor nucleus is closer to the floor plate and abnormally shaped

Genotype
MGI:5293367

cn13

• Allelic Composition: Egr2^tm2(cre)Pch/Egr2⁺; Phox2b^tm4Jbr/Phox2b⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * DBA/2

mortality/aging

mortality/aging ( J:176573 )

N • the great majority of mice survive to adulthood

nervous system

abnormal retrotrapezoid nucleus morphology ( J:176573 )

• massive depletion of retrotrapezoid nucleus neurons at P9

abnormal autonomic nervous system physiology ( J:176573 )

• frequency of rhythmic phrenic discharges is reduced and does not respond to acidification

respiratory system

abnormal respiratory function ( J:176573 )

• hypoxic response is more vigorous (increase in ventilation is more pronounced and lasts longer) compared to controls

• exposure to pure O2 triggers periodic breathing in mutants but not in controls

decreased pulmonary ventilation ( J:176573 )

• in normoxia mean ventilation is reduced due to longer breath duration

• complete absence of normal response to hypercapnia at P2 and P9

• at 3 weeks and 4 months of age mice display a reduced increase in ventilation in response to hypercapnia

homeostasis/metabolism

alkalemia ( J:176573 )

• slight but statistically significant increase in pH

Genotype
MGI:4418307

cn14

• Allelic Composition: Phox2b^tm3.1Jbr/Phox2b^tm3.1Jbr; Egr2^tm2(cre)Pch/Egr2⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * DBA/2

mortality/aging

postnatal lethality, complete penetrance ( J:155885 )

• 1 week after birth, mice are dead

nervous system

abnormal neuron differentiation ( J:155885 )

• mice exhibit impaired development of retrotapezoid nucleus neurons compared with wild-type mice

abnormal neuron physiology ( J:155885 )

• the parafacial area e-pF oscillator exhibits only occasional motor activity bursts with reduced frequency compared to in wild-type mice

• rhythmic phrenic discharges are less frequent than in wild-type mice

• mice fail to exhibit an accelerated respiratory-like rhythm phrenic discharge in response to low pH challenge unlike similarly treated wild-type mice

cellular

abnormal neuron differentiation ( J:155885 )

• mice exhibit impaired development of retrotapezoid nucleus neurons compared with wild-type mice

Genotype
MGI:5903403

cn15

• Allelic Composition: Crygn^{tm1a(EUCOMM)Wtsi}/Crygn^{tm1a(EUCOMM)Wtsi}; Egr2^tm2(cre)Pch/Egr2⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6N

nervous system

nervous system phenotype ( J:236916 )

N • mice exhibit no gross abnormalities in size or shape of all major nuclei of the superior olivary complex

abnormal pons morphology ( J:236916 )

• reduced volume of the medial nucleus of the trapezoid body (MNTB) at P25 due to reduced neuron numbers without a reduction in cross sectional area

• small reduction in the lateral superior olive

• however, MNTB volume is normal at P4

decreased neuron number ( J:236916 )

• in the medial nucleus of the trapezoid body

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:236916 )

N • mice exhibit a non-significant improvement in ABR thresholds for click and noise burst stimuli and DPOAE growth functions, amplitudes and thresholds

abnormal auditory brainstem response ( J:236916 )

• amplitudes of wave IV are increased above 50 dB compared with controls

• however, overall latencies of ABR peaks are normal